DeCure for Hemolytic anemia due to adenylate kinase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemolytic anemia due to adenylate kinase deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHemolytic anemia due to adenylate kinase deficiency maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for hemolytic anemia due to adenylate kinase deficiency is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
adenylate kinase 1 (AK1) — AK1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet adenosinedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2C95 · 1.71 Å · ligand BIS(ADENOSINE)-5'-TETRAPHOSPHATE (B4P). Experimental structure, not a prediction.
What the evidence adds up to
Adenylate kinase deficiency is a very rare cause of congenital haemolytic anaemia. One 1994 report describes six children from one family with the deficiency; three also had G6PD deficiency. In that family, homozygously affected individuals had haemoglobin levels of 8–9 g/dl, while those with combined G6PD deficiency had more severe anaemia with haemoglobin levels around 6 g/dl. The AK-deficient children in that family were also mentally retarded. Splenectomy in five of the six patients produced complete remission of the haemolytic process. An earlier 1983 case of a 10-year-old Japanese girl with red cell AK activity at 44% of normal showed moderate to mild haemolytic anaemia since the neonatal period, but her physical and mental development was normal. Her red cell glycolytic intermediates and adenine nucleotides were normal compared with a reticulocyte-rich control, and glucose consumption and lactate formation were normal. The patient’s enzyme had an increased Michaelis constant for adenosine diphosphate and slight thermal instability, and migrated between the AK 1 and AK 2 positions on electrophoresis.
A 2021 study identified a novel homozygous mutation, c.301C > A (p. Gln101Lys), in the AK1 gene in an Indian family, and performed the first prenatal diagnosis of AK deficiency in India. The report notes that only ten mutations in the AK1 gene had been described to date. The abstract does not give haemoglobin levels or clinical details for that patient, and the claim of mental and psychomotor retardation is described as occurring only in exceptional cases. A 1986 case report describes a 27-year-old patient with severe haemolytic anaemia and low levels of adenosine triphosphate and decreased pyruvate kinase activity, who developed acute myeloblastic leukaemia 20 months later; that case involved acquired enzyme deficiency in a preleukaemic state, not inherited adenylate kinase deficiency.
The evidence is limited to a handful of families and isolated case reports. No controlled trials exist. The natural history of the condition is not well characterised, and the relationship between genotype, enzyme activity level, and clinical severity remains unclear. What is missing is a systematic registry of patients, standardised assays for AK activity and mutation screening, and prospective data on the effect of splenectomy and on the reported association with neurodevelopmental impairment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 1994 · 39 citations
Congenital haemolytic anaemia associated with adenylate kinase deficiency
AbstractChronic haemolytic anaemia associated with adenylate kinase (AK) deficiency is very rare and only seven cases in five families have been described. We present six children of one family who are deficient of this enzyme and in three of them a combined G6PD deficiency was found. AK deficiency was transmitted by an autosomal recessive gene and heterozygous state was not accompanied by disease, whereas homozygously affected individuals present a congenital chronic non-spherocytic haemolytic anaemia with haemoglobin levels of 8-9 g/dl. Patients also deficient in G6PD suffer from a more severe haemolytic anaemia with haemoglobin levels around 6 g/dl. The AK-deficient children are also mentally retarded. Splenectomy performed in five of the six patients resulted in complete remission of the haemolytic process.
American Journal of Hematology · 1983 · 28 citations
Red cell adenylate kinase deficiency associated with hereditary nonspherocytic hemolytic anemia: Clinical and biochemical studies
AbstractWe report here a case of red cell adenylate kinase (AK) deficiency associated with hereditary hemolytic anemia. The proband is a 10-year-old Japanese girl. Her physical and mental development was normal. She has shown moderate to mild hemolytic anemia since the neonatal period and hepatosplenomegaly. The red cell AK activity was 44% of normal. Contents of red cell glycolytic intermediates and adenine nucleotides were normal when compared with a comparable reticulocyte-rich control. Glucose consumption and lactate formation were normal. Hexose monophosphate shunt activity was somewhat lower than that of a comparable reticulocyte-rich control. There were no significant differences in the contents of adenine nucleotides between the younger and older red cells of the patient. Enzymatic characterization by hemolysate revealed that the patient's AK had an increased Michaelis constant for adenosine diphosphate and slight thermal instability. The patient's enzyme migrated approximately half-way between the AK 1 and AK 2 position on starch-gel electrophoresis. The mode of inheritance of this case is obscure. The mechanism of hemolysis might be a structural gene mutation that caused altered electrophoretic and kinetic properties.
Archives of Internal Medicine · 1986 · 3 citations
Preleukemia manifested by hemolytic anemia with pyruvate-kinase deficiency
Abstract• A 27-year-old patient manifested severe hemolytic anemia during a preleukemia phase. Low levels of adenosine triphosphate and decreased activity of pyruvate kinase were found. Acute myeloblastic leukemia developed in this patient 20 months later. The case suggests that acquired enzyme deficiency may play a role in the development of anemia in the preleukemic state. (<i>Arch Intern Med</i>1986;146:785-786)
Rare hereditary nonspherocytic hemolytic anemia caused by a novel homozygous mutation, c.301C > A, (Q101K), in the AK1 gene in an Indian family
AbstractAbstract Background Adenylate kinase (AK) deficiency is a rare red cell enzymopathy associated with moderate to severe congenital nonspherocytic hemolytic anemia, along with mental and psychomotor retardation (in exceptional cases). Only ten mutations have been detected in the AK1 gene to date. In this study, we aimed to diagnose the unexplained issue of haemolytic anaemia and offer antenatal screening to the family. Methods Genomic DNA was isolated from whole blood by a standard protocol. Targeted next-generation sequencing (t-NGS) was performed to identify pathogenic variants in the patient and control samples. A chronic villus sample was collected at 11 weeks of gestation from the mother, and molecular testing was performed. Genetic confirmation was concluded by Sanger DNA sequencing. Bioinformatics tools predicted the pathogenicity of the variant. Results t-NGS revealed a homozygous variant (c.301C > A, p. Gln101Lys) in the AK1 gene in the patient and heterozygosity in the fetus and parental samples. The prediction tools SIFT, Polyphen2, Provean, PMUT, Mutation taster, and Mutation Assessor, confirmed the damaging effect of the variant on the AK1 protein structure Conclusion We have presented a novel mutation in the AK1 gene (p. Gln101Lys) associated with adenylate kinase deficiency. It is the first prenatal diagnosis of AK deficiency in India, where heterogeneity is exceptionally high.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
